Exercise training as a treatment strategy for improved cardiac metabolism in patients with heart failure and with a transplanted heart

The search for an adequate treatment for heart failure is a major challenge, and even though the medical treatment has been improved substantially in recent years, the mortality rate remains high. During the last decades physical activity has been recogni zed as an important part in the rehabilitation of these patients groups. Recent data in animal models of heart failure point to energy starvation as a central part of impaired cardiac function, but its harmful effects on contractile mechanisms has never b een studied in intact myocardium from man. To optimize the treatment there is need of a better understanding of the underlying myocardial mechanisms for the disease in humans (not only in animal models), as well as the beneficial effects of physical activ ity on the myocardium. Understanding the cellular and molecular mechanisms of training-induced amelioration of cardiac performance in man will help identify molecular targets for improved treatment and prevention of cardiovascular disease. The main focu s of the present 3-year post doctoral project is twofold: I) To determine to what degree myocardial energy metabolism is linked to impaired function in human cardiomyocytes, whether exercise training can restore cardiomyocyte function and whether this is linked to improved mitochondrial function, and II) To determine exercise-induced changes in energy metabolism, cellular and molecular adaptation in cardiomyocytes from patients that has undergone heart transplantation.